The International Continence Society (ICS) has defined overactive bladder (OAB) as a symptom complex of urgency, with or without urge incontinence, accompanied by frequency and nocturia. The symptoms of overactive bladder are usually associated with involuntary contractions of the detrusor (bladder) muscle thus creating a state of bladder hyperactivity. OAB is commonly classified into subtypes including neurogenic, idiopathic, and outlet obstruction. Neurogenic DAB is attributed to coexisting neurological conditions such as Parkinson's disease, multiple sclerosis, spinal cord injury or stroke. The underlying pathophysiology is the interruption of the otherwise orderly control of micturition, resulting in the symptom complex described above. The cause of idiopathic OAB is not as well defined; alterations in signalling within the bladder have been implicated. Finally, OAB may be associated with anatomical changes in the lower urinary tract, for example, in patients with bladder outlet obstruction, which may be the result of an enlarged prostate gland. Overall, the incidence of OAB increases with age. The ratio of men to women affected depends on the age group, but in general women tend to be more affected than men. OAB represents a significant quality of life burden to patients.
Muscarinic receptor antagonists (also known as antimuscarinics or anticholinergics) such as Detrol® LA (tolterodine), Ditropan XL® (oxybutynin), and Vesicare® (solifenacin succinate) currently represent the major pharmacological options approved and marketed for the treatment of OAB. Antimuscarinics are believed to reduce bladder overactivity by inhibiting bladder smooth muscle contractility. Physicians and patients remain unsatisfied with the current therapies and desire medicines with improved efficacy and tolerability. In particular there is an unacceptably high incidence of side effects, including dry mouth and constipation associated with these medications. Also, current medications do not adequately treat urgency, one of the most bothersome symptoms of OAB.
Accordingly, there remains a need for new medicines and methods of treatment that offer improved efficacy and tolerability in the treatment of symptoms associated with overactive bladder, above and beyond the currently available therapies.